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Vaccines, Volume 8, Issue 4 (December 2020) – 228 articles

Cover Story (view full-size image): A human or nonhuman adenoviral (Ad) vector-based vaccine platform is a versatile egg-independent and cost-effective approach for generating large numbers of influenza vaccine doses in a short timeframe. The activation of innate immunity by the Ad vector induces broad, durable, and protective influenza-specific humoral and cell-mediated immune responses. Due to the availability of less-prevalent human Ad vectors and nonhuman Ad vectors as vaccine platforms, there will be a minimal impact of preexisting Ad vector immunity on vaccine efficacy. An Ad vector-based vaccine platform is well suited for designing effective vaccines not only for seasonal and pandemic influenza but also for other infectious diseases. View this paper.
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Communication
Protection against the New Equine Influenza Virus Florida Clade I Outbreak Strain Provided by a Whole Inactivated Virus Vaccine
Vaccines 2020, 8(4), 784; https://doi.org/10.3390/vaccines8040784 - 21 Dec 2020
Cited by 1 | Viewed by 897
Abstract
Equine influenza virus (EIV) is a major cause of respiratory disease in horses. Vaccination is an effective tool for infection control. Although various EIV vaccines are widely available, major outbreaks occurred in Europe in 2018 involving a new EIV H3N8 FC1 strain. In [...] Read more.
Equine influenza virus (EIV) is a major cause of respiratory disease in horses. Vaccination is an effective tool for infection control. Although various EIV vaccines are widely available, major outbreaks occurred in Europe in 2018 involving a new EIV H3N8 FC1 strain. In France, it was reported that both unvaccinated and vaccinated horses were affected despite >80% vaccination coverage and most horses being vaccinated with a vaccine expressing FC1 antigen. This study assessed whether vaccine type, next to antigenic difference between vaccine and field strain, plays a role. Horses were vaccinated with an ISCOMatrix-adjuvanted, whole inactivated virus vaccine (Equilis Prequenza) and experimentally infected with the new FC1 outbreak strain. Serology (HI), clinical signs, and virus shedding were evaluated in vaccinated compared to unvaccinated horses. Results showed a significant reduction in clinical signs and a lack of virus shedding in vaccinated horses compared to unvaccinated controls. From these results, it can be concluded that Equilis Prequenza provides a high level of protection to challenge with the new FC1 outbreak strain. This suggests that, apart from antigenic differences between vaccine and field strain, other aspects of the vaccine may also play an important role in determining field efficacy. Full article
(This article belongs to the Section Veterinary Vaccines)
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Review
Harnessing Cellular Immunity for Vaccination against Respiratory Viruses
Vaccines 2020, 8(4), 783; https://doi.org/10.3390/vaccines8040783 - 21 Dec 2020
Cited by 8 | Viewed by 2058
Abstract
Severe respiratory viral infections, such as influenza, metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus (RV), and coronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause significant mortality and morbidity worldwide. These viruses have been identified as important causative agents of acute respiratory disease [...] Read more.
Severe respiratory viral infections, such as influenza, metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus (RV), and coronaviruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cause significant mortality and morbidity worldwide. These viruses have been identified as important causative agents of acute respiratory disease in infants, the elderly, and immunocompromised individuals. Clinical signs of infection range from mild upper respiratory illness to more serious lower respiratory illness, including bronchiolitis and pneumonia. Additionally, these illnesses can have long-lasting impact on patient health well beyond resolution of the viral infection. Aside from influenza, there are currently no licensed vaccines against these viruses. However, several research groups have tested various vaccine candidates, including those that utilize attenuated virus, virus-like particles (VLPs), protein subunits, and nanoparticles, as well as recent RNA vaccines, with several of these approaches showing promise. Historically, vaccine candidates have advanced, dependent upon the ability to activate the humoral immune response, specifically leading to strong B cell responses and neutralizing antibody production. More recently, it has been recognized that the cellular immune response is also critical in proper resolution of viral infection and protection against detrimental immunopathology associated with severe disease and therefore, must also be considered when analyzing the efficacy and safety of vaccine candidates. These candidates would ideally result in robust CD4+ and CD8+ T cell responses as well as high-affinity neutralizing antibody. This review will aim to summarize established and new approaches that are being examined to harness the cellular immune response during respiratory viral vaccination. Full article
(This article belongs to the Special Issue Virus-Like Particle & Nanoparticle Vaccines against Viral Infections)
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Article
Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies
Vaccines 2020, 8(4), 782; https://doi.org/10.3390/vaccines8040782 - 21 Dec 2020
Viewed by 827
Abstract
To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of [...] Read more.
To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4+ T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in in vitro studies, an issue that could impact HIV-1 vaccine design strategies. Full article
(This article belongs to the Section HIV Vaccines)
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Article
Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin
Vaccines 2020, 8(4), 781; https://doi.org/10.3390/vaccines8040781 - 20 Dec 2020
Viewed by 1064
Abstract
Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in [...] Read more.
Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in embryonated chicken eggs-based vaccine production system, they need to be improved in terms of immunogenicity and potential mammalian pathogenicity. We replaced the PB2 gene alone or the PB2 (polymerase basic protein 2), NP (nucleoprotein), M (matrix protein) and NS (non-structural protein) genes together in the PR8 strain with corresponding genes from AIVs with low pathogenicity to remove mammalian pathogenicity and to match CD8+ T cell epitopes with contemporary HPAI viruses, respectively, without loss of viral fitness. Additionally, we tested the effect of the H103Y mutation of hemagglutinin (HA) on antigen productivity, mammalian pathogenicity and heat/acid stability. The replacement of PB2 genes and the H103Y mutation reduced the mammalian pathogenicity but increased the antigen productivity of the recombinant vaccine strains. The H103Y mutation increased heat stability but unexpectedly decreased acid stability, probably resulting in increased activation pH for HA. Interestingly, vaccination with inactivated recombinant virus with replaced NP, M and NS genes halted challenge virus shedding earlier than the recombinant vaccine without internal genes replacement. In conclusion, we successfully generated recombinant clade 2.3.4.4c H5N6 vaccine strains that were less pathogenic to mammals and more productive and heat stable than conventional PR8-derived recombinant strains by optimization of internal genes and the H103Y mutation of HA. Full article
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
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Article
Universal Single-Dose Vaccination against Hepatitis A in Children in a Region of High Endemicity
Vaccines 2020, 8(4), 780; https://doi.org/10.3390/vaccines8040780 - 20 Dec 2020
Cited by 3 | Viewed by 998
Abstract
Since August 2012, universal single-dose vaccination in children aged at least three years has been implemented in the Republic of Tuva, which was previously the region most affected by hepatitis A in Russia. The objective of this cross-sectional study was the assessment of [...] Read more.
Since August 2012, universal single-dose vaccination in children aged at least three years has been implemented in the Republic of Tuva, which was previously the region most affected by hepatitis A in Russia. The objective of this cross-sectional study was the assessment of the immunological and epidemiological effectiveness of vaccination program five years following its implementation. In the pre-vaccination period, anti-HAV antibody detection rates in Tuva was 66.0% [95% CI: 56.3–74.6%] in children aged 10–14 years and reached a plateau (>95%) by age 20–29 years. Annual incidence rates in children under 18 years of age peaked at 450–860 per 100,000 in pre-vaccination years but dropped to 7.5 per 100,000 in this age group and to 3.2 per 100,000 in the total population one year after the start of vaccination. Since 2016, no cases of hepatitis A has been reported in Tuva. Serum anti-HAV antibodies were quantified in samples from healthy children following single-dose vaccination. Protective anti-HAV antibody concentrations (≥10 mIU/mL) were detected in 98.0% (95% CI: 96.2–99.0% (442/451)) of children tested one month after single-dose immunization, in 93.5% (95% CI: 91.0–95.4% (477/510)) and in 91.1% (95% CI: 88.2–93.4% (422/463)) of children one year and five years after single-dose immunization, respectively. Anti-HAV antibody geometric mean concentrations were similar in sera collected one month, one year, and five years following single-dose vaccination: 40.24 mIU/mL, 44.96 mIU/mL, and 57.73 mIU/mL, respectively (p > 0.05). These data confirm that single-dose vaccination is an effective method of bringing hepatitis A under control in a short period of time in a highly endemic region. Full article
(This article belongs to the Special Issue Perspective Technologies of Vaccination and Immunotherapy)
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Review
Environmental Risk Assessment for rVSVΔG-ZEBOV-GP, a Genetically Modified Live Vaccine for Ebola Virus Disease
Vaccines 2020, 8(4), 779; https://doi.org/10.3390/vaccines8040779 - 19 Dec 2020
Cited by 3 | Viewed by 1495
Abstract
rVSVΔG-ZEBOV-GP is a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine for the prevention of Ebola virus disease caused by Zaire ebolavirus. As a replication-competent genetically modified organism, rVSVΔG-ZEBOV-GP underwent various environmental evaluations prior to approval, the most in-depth being the environmental [...] Read more.
rVSVΔG-ZEBOV-GP is a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine for the prevention of Ebola virus disease caused by Zaire ebolavirus. As a replication-competent genetically modified organism, rVSVΔG-ZEBOV-GP underwent various environmental evaluations prior to approval, the most in-depth being the environmental risk assessment (ERA) required by the European Medicines Agency. This ERA, as well as the underlying methodology used to arrive at a sound conclusion about the environmental risks of rVSVΔG-ZEBOV-GP, are described in this review. Clinical data from vaccinated adults demonstrated only infrequent, low-level shedding and transient, low-level viremia, indicating a low person-to-person infection risk. Animal data suggest that it is highly unlikely that vaccinated individuals would infect animals with recombinant virus vaccine or that rVSVΔG-ZEBOV-GP would spread within animal populations. Preclinical studies in various hematophagous insect vectors showed that these species were unable to transmit rVSVΔG-ZEBOV-GP. Pathogenicity risk in humans and animals was found to be low, based on clinical and preclinical data. The overall risk for non-vaccinated individuals and the environment is thus negligible and can be minimized further through defined mitigation strategies. This ERA and the experience gained are relevant to developing other rVSV-based vaccines, including candidates under investigation for prevention of COVID-19. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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Article
SARS-CoV-2 Seroprevalence Survey in People Involved in Different Essential Activities during the General Lock-Down Phase in the Province of Prato (Tuscany, Italy)
Vaccines 2020, 8(4), 778; https://doi.org/10.3390/vaccines8040778 - 19 Dec 2020
Cited by 9 | Viewed by 1535
Abstract
Serosurveys may help to assess the transmission dynamics in high-risk groups. The aim of the study was to assess the SARS-CoV-2 antibody seroprevalence in people who had performed essential activities during the lock-down period in the Province of Prato (Italy), and to evaluate [...] Read more.
Serosurveys may help to assess the transmission dynamics in high-risk groups. The aim of the study was to assess the SARS-CoV-2 antibody seroprevalence in people who had performed essential activities during the lock-down period in the Province of Prato (Italy), and to evaluate the risk of exposure to SARS-CoV-2 according to the type of service. All the workers and volunteers of the Civil Protection, employees of the municipalities, and all the staff of the Health Authority of the Province of Prato were invited to be tested with a rapid serological test. A total of 4656 participants were tested. SARS-CoV-2 antibodies were found in 138 (2.96%) cases. The seroprevalence in health care workers, in participants involved in essential support services and in those who worked from home were 4.1%, 1.4% and 1.0%, respectively. Health care workers experienced higher odds of seropositivity (OR 4.38, 95%CI 2.19–10.41) than participants who were assigned to work-from-home; no significant seropositivity differences were observed between support services and work-from-home groups. A low circulation of SARS-CoV-2 was observed among participants performing different essential activities. Findings highlighted the risk of in-hospital transmission in healthcare workers and that community support services may increase the risk of seropositivity to a limited extent in low incidence areas. Full article
(This article belongs to the Special Issue SARS-CoV-2 Serological Studies around the Globe)
Article
Activation of Soluble Polysaccharides with 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate (CDAP) for Use in Protein–Polysaccharide Conjugate Vaccines and Immunological Reagents. III Optimization of CDAP Activation
Vaccines 2020, 8(4), 777; https://doi.org/10.3390/vaccines8040777 - 18 Dec 2020
Cited by 3 | Viewed by 1260
Abstract
CDAP (1-cyano-4-dimethylaminopyridine tetrafluoroborate) is employed in the synthesis of conjugate vaccines as a cyanylating reagent. In the published method, which used pH 9 activation at 20 °C (Vaccine, 14:190, 1996), the rapid reaction made the process difficult to control. Here, we [...] Read more.
CDAP (1-cyano-4-dimethylaminopyridine tetrafluoroborate) is employed in the synthesis of conjugate vaccines as a cyanylating reagent. In the published method, which used pH 9 activation at 20 °C (Vaccine, 14:190, 1996), the rapid reaction made the process difficult to control. Here, we describe optimizing CDAP activation using dextran as a model polysaccharide. CDAP stability and reactivity were determined as a function of time, pH and temperature. While the rate of dextran activation was slower at lower pH and temperature, it was balanced by the increased stability of CDAP, which left more reagent available for reaction. Whereas maximal activation took less than 2.5 min at pH 9 and 20 °C, it took 10–15 min at 0 °C. At pH 7 and 0 °C, the optimal time increased to >3 h to achieve a high level of activation. Many buffers interfered with CDAP activation, but DMAP could be used to preadjust the pH of polysaccharide solutions so that the pH only needed to be maintained. We found that the stability of the activated dextran was relatively independent of pH over the range of pH 1–9, with the level of activation decreased by 40–60% over 2 h. The use of low temperature and a less basic pH, with an optimum reaction time, requires less CDAP, improving activation levels while making the process more reliable and easier to scale up. Full article
(This article belongs to the Special Issue Carbohydrate Immunogens in Vaccines)
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Review
Neo-Antigen mRNA Vaccines
Vaccines 2020, 8(4), 776; https://doi.org/10.3390/vaccines8040776 - 18 Dec 2020
Cited by 13 | Viewed by 3081
Abstract
The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. [...] Read more.
The interest in therapeutic cancer vaccines has caught enormous attention in recent years due to several breakthroughs in cancer research, among which the finding that successful checkpoint blockade treatments reinvigorate neo-antigen-specific T cells and that successful adoptive cell therapies are directed towards neo-antigens. Neo-antigens are cancer-specific antigens, which develop from somatic mutations in the cancer cell genome that can be highly immunogenic and are not subjected to central tolerance. As the majority of neo-antigens are unique to each patient’s cancer, a vaccine technology that is flexible and potent is required to develop personalized neo-antigen vaccines. In vitro transcribed mRNA is such a technology platform and has been evaluated for delivery of neo-antigens to professional antigen-presenting cells both ex vivo and in vivo. In addition, strategies that support the activity of T cells in the tumor microenvironment have been developed. These represent a unique opportunity to ensure durable T cell activity upon vaccination. Here, we comprehensively review recent progress in mRNA-based neo-antigen vaccines, summarizing critical milestones that made it possible to bring the promise of therapeutic cancer vaccines within reach. Full article
(This article belongs to the Special Issue The Past, Present, and Future of mRNA Vaccines)
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Review
The Potential of Soluble Human Leukocyte Antigen Molecules for Early Cancer Detection and Therapeutic Vaccine Design
Vaccines 2020, 8(4), 775; https://doi.org/10.3390/vaccines8040775 - 18 Dec 2020
Viewed by 1217
Abstract
Human leukocyte antigen (HLA) molecules are essential for anti-tumor immunity, as they display tumor-derived peptides to drive tumor eradication by cytotoxic T lymphocytes. HLA molecules are primarily studied as peptide-loaded complexes on cell membranes (mHLA) and much less attention is given to their [...] Read more.
Human leukocyte antigen (HLA) molecules are essential for anti-tumor immunity, as they display tumor-derived peptides to drive tumor eradication by cytotoxic T lymphocytes. HLA molecules are primarily studied as peptide-loaded complexes on cell membranes (mHLA) and much less attention is given to their secretion as soluble HLA–peptide complexes (sHLA) into bodily fluids. Yet sHLA levels are altered in various pathologies including cancer, and are thus of high interest as biomarkers. Disconcordance in results across studies, however, hampers interpretation and generalization of the relationship between sHLA levels and cancer presence, thereby impairing its use as a biomarker. Furthermore, the question remains to what extent sHLA complexes exert immunomodulatory effects and whether shifts in sHLA levels contribute to disease or are only a consequence of disease. sHLA complexes can also bear tumor-derived peptides and recent advancements in mass spectrometry now permit closer sHLA peptide cargo analysis. sHLA peptide cargo may represent a “liquid biopsy” that could facilitate the use of sHLA for cancer diagnosis and target identification for therapeutic vaccination. This review aims to outline the contradictory and unexplored aspects of sHLA and to provide direction on how the full potential of sHLA as a quantitative and qualitative biomarker can be exploited. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Advances and Future Prospects)
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Article
Knowledge and Attitudes on Vaccination in Southern Romanians: A Cross-Sectional Questionnaire
Vaccines 2020, 8(4), 774; https://doi.org/10.3390/vaccines8040774 - 18 Dec 2020
Cited by 7 | Viewed by 3573
Abstract
Vaccines are fundamental instruments upon which all modern medicine is hinged. This has recently come into the light because of the COVID-19 pandemic caused by SARS-CoV-2. We aimed to assess the knowledge and attitudes of the public regarding vaccination. To this end, a [...] Read more.
Vaccines are fundamental instruments upon which all modern medicine is hinged. This has recently come into the light because of the COVID-19 pandemic caused by SARS-CoV-2. We aimed to assess the knowledge and attitudes of the public regarding vaccination. To this end, a questionnaire, which was disseminated to the general population between 2017 and 2019, was used. We evaluated the responses from 1647 individuals (61% female, with a median age of 37 years, mostly from urban settings). Most respondents (85%) had children and were in favor of vaccination. Our study underlines the role that family physicians have in the education and information of citizens. A small, but considerable, number of respondents (108, 7.84% of those with children) had not vaccinated their children according to the national vaccination scheme. Deterrents were considered to be lack of information and fear of side effects. However, 167 of our respondents (12.12% out of 1377 respondents with children) said that their child experienced adverse events—most of which were mild local reactions. Alternatives to vaccination were proposed by some. In this study, we highlight the attitudes of respondents and multiple gaps in general knowledge, both of which may need to be addressed, especially in light of the current pandemic situation and past failed campaigns. Full article
(This article belongs to the Special Issue Strategies to Increase Vaccination Coverage and Vaccine Confidence)
Review
Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases
Vaccines 2020, 8(4), 773; https://doi.org/10.3390/vaccines8040773 - 17 Dec 2020
Cited by 9 | Viewed by 866
Abstract
Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for [...] Read more.
Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics. Full article
Article
Occurrence of Antibodies against SARS-CoV-2 in the Domestic Cat Population of Germany
Vaccines 2020, 8(4), 772; https://doi.org/10.3390/vaccines8040772 - 17 Dec 2020
Cited by 25 | Viewed by 2108
Abstract
Domestic cats (Felis catus) are popular companion animals that live in close contact with their human owners. Therefore, the risk of a trans-species spreading event between domestic cats and humans is ever-present. Shortly after the emergence of the severe acute respiratory [...] Read more.
Domestic cats (Felis catus) are popular companion animals that live in close contact with their human owners. Therefore, the risk of a trans-species spreading event between domestic cats and humans is ever-present. Shortly after the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread around the world, the role of domestic cats in the transmission cycle was questioned. In the present study, the first large-scale survey of antibody occurrence in the domestic cat population in Germany was conducted, in order to assess the incidence of naturally occurring human to cat transmission of SARS-CoV-2. A total of 920 serum samples, which were collected from April to September of 2020, were screened by an indirect multispecies ELISA. Positive samples were verified using an indirect immunofluorescence test (iIFT) and additionally tested for neutralizing antibodies. Furthermore, serum samples were screened for antibodies against feline coronavirus (FCoV), in order to rule out cross-reactivity in the described test systems. Overall, 0.69% (6/920) of serum samples were found to be positive for antibodies against SARS-CoV-2 by ELISA and iIFT. Two of these reactive sera also displayed neutralizing antibodies. No cross-reactivity with FCoV-specific antibodies was observed. The finding of SARS-CoV-2 antibody-positive serum samples in the domestic cat population of Germany, during a period when the incidence of human infection in the country was still rather low, indicates that human-to-cat transmission of SARS-CoV-2 happens, but there is no indication of SARS-CoV-2 circulation in cats. Full article
(This article belongs to the Special Issue SARS-CoV-2 Serological Studies around the Globe)
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Article
A Newcastle Disease Virus (NDV) Expressing a Membrane-Anchored Spike as a Cost-Effective Inactivated SARS-CoV-2 Vaccine
Vaccines 2020, 8(4), 771; https://doi.org/10.3390/vaccines8040771 - 17 Dec 2020
Cited by 16 | Viewed by 5422
Abstract
A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based [...] Read more.
A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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Article
A Review of Adherence and Predictors of Adherence to the CONSORT Statement in the Reporting of Tuberculosis Vaccine Trials
Vaccines 2020, 8(4), 770; https://doi.org/10.3390/vaccines8040770 - 16 Dec 2020
Viewed by 855
Abstract
The statement on Consolidated Standards of Reporting Trials (CONSORT) ensures transparency in the reporting of randomized trials. However, it is unclear if the statement has led to improvement in the quality of reporting of tuberculosis (TB) vaccine trials. We explored the quality of [...] Read more.
The statement on Consolidated Standards of Reporting Trials (CONSORT) ensures transparency in the reporting of randomized trials. However, it is unclear if the statement has led to improvement in the quality of reporting of tuberculosis (TB) vaccine trials. We explored the quality of reporting of TB vaccine trials according to the latest version of the CONSORT statement, released in 2010. We searched PubMed and the Cochrane Central Register of Controlled Trials in August 2019. We conducted screening, study selection, and data extraction in duplicate; and resolved differences through discussion. We assessed reporting to be adequate if trials reported at least 75% of the CONSORT 2010 items. We conducted a trend analysis to assess if there was improvement in reporting over time. We also used logistic regression to assess factors associated with adequate reporting. We included 124 trials in the analyses. The mean proportion of adherence was 67.3% (95% confidence interval 64.4% to 70.1%), with only 46 (37%) trials having adequate reporting. There was a significant improvement in the quality of reporting over time (p < 0.0001). Trials published in journals with impact factors between 10 and 20 were more likely to have adequate reporting (odds ratio 9.4; 95% confidence interval 1.30 to 67.8), compared to lower-impact-factor journals. Despite advances over time, the reporting of TB vaccine trials is still inadequate and requires improvement. Full article
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Review
Immune Response to Vaccination in Patients with Psoriasis Treated with Systemic Therapies
Vaccines 2020, 8(4), 769; https://doi.org/10.3390/vaccines8040769 - 16 Dec 2020
Cited by 10 | Viewed by 1745
Abstract
Psoriasis is a chronic inflammatory skin disease usually treated with immunomodulatory/immunosuppressive agents. The use of these agents has been associated with an increased susceptibility to infections. Vaccination might represent a critical aspect in the management of patients with psoriasis treated with immunomodulatory/immunosuppressive therapies. [...] Read more.
Psoriasis is a chronic inflammatory skin disease usually treated with immunomodulatory/immunosuppressive agents. The use of these agents has been associated with an increased susceptibility to infections. Vaccination might represent a critical aspect in the management of patients with psoriasis treated with immunomodulatory/immunosuppressive therapies. This narrative review aimed to provide an overview on the immune response to vaccines in subjects treated with systemic agents used to treat patients with moderate to severe psoriasis. Publications appearing in PubMed, Scopus, and ISI–Web of Knowledge database were selected using Medical Subject Headings key terms. Overall, published data confirmed that vaccination with attenuated live vaccines during therapy with immunomodulatory/immunosuppressive therapies should be avoided. For nonlive vaccines, a more favorable safety profile of biologic agents compared to conventional systemic agents is described as the humoral response to vaccines is in general well-preserved. Treatment with cyclosporine and methotrexate is associated with lower antibody titers to vaccines, and thus these agents are better discontinued during vaccination. In contrast, treatment with biological agents is not associated with lower antibody response and can thus be continued safely. Full article
Article
Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness
Vaccines 2020, 8(4), 768; https://doi.org/10.3390/vaccines8040768 - 16 Dec 2020
Cited by 2 | Viewed by 1108
Abstract
H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to [...] Read more.
H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus. Full article
(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)
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Article
Distinct African Swine Fever Virus Shedding in Wild Boar Infected with Virulent and Attenuated Isolates
Vaccines 2020, 8(4), 767; https://doi.org/10.3390/vaccines8040767 - 16 Dec 2020
Cited by 4 | Viewed by 1578
Abstract
Since the reappearance of African swine fever virus (ASFV), the disease has spread in an unprecedented animal pandemic in Eurasia. ASF currently constitutes the greatest global problem for the swine industry. The wild boar (Sus scrofa) in which the pathogen has [...] Read more.
Since the reappearance of African swine fever virus (ASFV), the disease has spread in an unprecedented animal pandemic in Eurasia. ASF currently constitutes the greatest global problem for the swine industry. The wild boar (Sus scrofa) in which the pathogen has established wild self-sustaining cycles, is a key reservoir for ASFV, signifying that there is an urgent need to develop an effective vaccine against this virus. Current scientific debate addresses whether live attenuated vaccines (LAVs), which have shown promising results in cross-protection of susceptible hosts, may be feasible for vaccinations carried out owing to safety concerns. The objective of this study was, therefore, to compare the ASFV shedding in wild boar infected with virulent and attenuated (LAV) isolates. Different shedding routes (oral fluid and feces) and viremia rates were characterized in wild boar inoculated with Lv17/WB/Rie1 isolate (n = 12) when compared to those inoculated with the virulent Armenia07 isolate (n = 17). In general, fewer animals infected with the Lv17/WB/Rie1 isolate tested positive for ASFV in blood, oral fluid, and feces in comparison to animals infected with the virulent Armenia07 isolate. The shedding patterns were characterized in order to understand the transmission dynamics. This knowledge will help evaluate the shedding of new LAV candidates in wild boar populations, including the comparison with gene deletion mutant LAVs, whose current results are promising. Full article
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Article
Vaccination Criteria Based on Factors Influencing COVID-19 Diffusion and Mortality
Vaccines 2020, 8(4), 766; https://doi.org/10.3390/vaccines8040766 - 15 Dec 2020
Cited by 2 | Viewed by 1840
Abstract
SARS-CoV-2 is highly contagious, rapidly turned into a pandemic, and is causing a relevant number of critical to severe life-threatening COVID-19 patients. However, robust statistical studies of a large cohort of patients, potentially useful to implement a vaccination campaign, are rare. We analyzed [...] Read more.
SARS-CoV-2 is highly contagious, rapidly turned into a pandemic, and is causing a relevant number of critical to severe life-threatening COVID-19 patients. However, robust statistical studies of a large cohort of patients, potentially useful to implement a vaccination campaign, are rare. We analyzed public data of about 19,000 patients for the period 28 February to 15 May 2020 by several mathematical methods. Precisely, we describe the COVID-19 evolution of a number of variables that include age, gender, patient’s care location, and comorbidities. It prompts consideration of special preventive and therapeutic measures for subjects more prone to developing life-threatening conditions while affording quantitative parameters for predicting the effects of an outburst of the pandemic on public health structures and facilities adopted in response. We propose a mathematical way to use these results as a powerful tool to face the pandemic and implement a mass vaccination campaign. This is done by means of priority criteria based on the influence of the considered variables on the probability of both death and infection. Full article
(This article belongs to the Special Issue Vaccines: Uptake and Equity in Times of the COVID-19 Pandemic)
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Article
Virus-Like Particle Based Vaccines Elicit Neutralizing Antibodies against the HIV-1 Fusion Peptide
Vaccines 2020, 8(4), 765; https://doi.org/10.3390/vaccines8040765 - 15 Dec 2020
Cited by 4 | Viewed by 1247
Abstract
Broadly neutralizing antibodies (bnAbs) isolated from HIV-infected individuals delineate vulnerable sites on the HIV envelope glycoprotein that are potential vaccine targets. A linear epitope within the N-terminal region of the HIV-1 fusion peptide (FP8) is the primary target of VRC34.01, a bnAb that [...] Read more.
Broadly neutralizing antibodies (bnAbs) isolated from HIV-infected individuals delineate vulnerable sites on the HIV envelope glycoprotein that are potential vaccine targets. A linear epitope within the N-terminal region of the HIV-1 fusion peptide (FP8) is the primary target of VRC34.01, a bnAb that neutralizes ~50% of primary HIV isolates. FP8 has attracted attention as a potential HIV vaccine target because it is a simple linear epitope. Here, platform technologies based on RNA bacteriophage virus-like particles (VLPs) were used to develop multivalent vaccines targeting the FP8 epitope. Both recombinant MS2 VLPs displaying the FP8 peptide and Qβ VLPs displaying chemically conjugated FP8 peptide induced high titers of FP8-specific antibodies in mice. Moreover, a heterologous prime-boost-boost regimen employing the two FP8-VLP vaccines and native envelope trimer was the most effective approach for eliciting HIV-1 neutralizing antibodies. Given the potent immunogenicity of VLP-based vaccines, this vaccination strategy—inspired by bnAb-guided epitope mapping, VLP bioengineering, and prime-boost immunization approaches—may be a useful strategy for eliciting bnAb responses against HIV. Full article
(This article belongs to the Special Issue HIV Vaccine)
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Review
A Comprehensive Review of the Immunological Response against Foot-and-Mouth Disease Virus Infection and Its Evasion Mechanisms
Vaccines 2020, 8(4), 764; https://doi.org/10.3390/vaccines8040764 - 14 Dec 2020
Cited by 1 | Viewed by 948
Abstract
Foot-and-mouth disease (FMD) is a highly contagious viral disease, which has been reported for over 100 years, and against which the struggle has lasted for the same amount of time. It affects individuals from the order Artiodactyla, such as cattle, swine, sheep, wild [...] Read more.
Foot-and-mouth disease (FMD) is a highly contagious viral disease, which has been reported for over 100 years, and against which the struggle has lasted for the same amount of time. It affects individuals from the order Artiodactyla, such as cattle, swine, sheep, wild animals from this order, and a few non-cloven hoofed species, such as mice and elephants. FMD causes large-scale economic losses for agricultural production systems; morbidity is almost 100% in an affected population, accompanied by a high mortality rate in young animals due to myocarditis or an inability to suckle if a mother is ill. The aetiological agent is an Aphthovirus from the family Picornaviridae, having seven serotypes: A, O, C, SAT1, SAT2, SAT3, and Asia 1. Serotype variability means that an immune response is serospecific and vaccines are thus designed to protect against each serotype independently. A host’s adaptive immune response is key in defence against pathogens; however, this virus uses successful strategies (along with most microorganisms) enabling it to evade a host’s immune system to rapidly and efficiently establish itself within such host, and thus remain there. This review has been aimed at an in-depth analysis of the immune response in cattle and swine regarding FMD virus, the possible evasion mechanisms used by the virus and describing some immunological differences regarding these species. Such aspects can provide pertinent knowledge for developing new FMD control and prevention strategies. Full article
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Article
Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes
Vaccines 2020, 8(4), 763; https://doi.org/10.3390/vaccines8040763 - 14 Dec 2020
Cited by 8 | Viewed by 1394
Abstract
African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant [...] Read more.
African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant impact on China’s pig and related industries. A safe and effective vaccine is needed to prevent and control the disease. Several gene-deleted ASFVs have been reported; however, none of them is safe enough and commercially available. In this study, we report the generation of a double gene-deleted ASFV mutant, ASFV-SY18-∆CD2v/UK, from a highly virulent field strain ASFV-SY18 isolated in China. The results showed that ASFV-SY18-∆CD2v/UK lost hemadsorption properties, and the simultaneous deletion of the two genes did not significantly affect the in vitro replication of the virus in primary porcine alveolar macrophages. Furthermore, ASFV-SY18-∆CD2v/UK was attenuated in pigs. All the ASFV-SY18-∆CD2v/UK-inoculated pigs remained healthy, and none of them developed ASF-associated clinical signs. Additionally, the ASFV-SY18-∆CD2v/UK-infected pigs developed ASFV-specific antibodies, and no virus genome was detected in blood and nasal discharges at 21 and 28 days post-inoculation. More importantly, we found that all the pigs inoculated with 104 TCID50 of ASFV-SY18-∆CD2v/UK were protected against the challenge with the parental ASFV-SY18. However, low-level ASFV DNA was detected in blood, nasal swabs, and lymphoid tissue after the challenge. The results demonstrate that ASFV-SY18-∆CD2v/UK is safe and able to elicit protective immune response in pigs and can be a potential vaccine candidate to control ASF. Full article
(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)
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Article
Novel Inactivated Subtype B Avian Metapneumovirus Vaccine Induced Humoral and Cellular Immune Responses
Vaccines 2020, 8(4), 762; https://doi.org/10.3390/vaccines8040762 - 14 Dec 2020
Cited by 1 | Viewed by 818
Abstract
Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain [...] Read more.
Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain LN16. Combined with a novel adjuvant containing immune-stimulating complexes (ISCOMs), the novel vaccine could induce high virus-specific and VN antibodies. In addition, it activated B and T lymphocytes and promoted the expression of IL-4 and IFN-γ. Importantly, boosting vaccination with the inactivated aMPV/B vaccine could provide 100% protection against aMPV/B infection with reduced virus shedding and turbinate inflammation. The protection efficacy could last for at least 6 months. This study yielded a novel inactivated aMPV/B vaccine that could serve as the first vaccine candidate in China, thus contributing to the control of aMPV/B and promoting the development of the poultry industry. Full article
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Article
Is a COVID-19 Vaccine Likely to Make Things Worse?
Vaccines 2020, 8(4), 761; https://doi.org/10.3390/vaccines8040761 - 14 Dec 2020
Cited by 4 | Viewed by 3228
Abstract
In order to limit the disease burden and economic costs associated with the COVID-19 pandemic, it is important to understand how effective and widely distributed a vaccine must be in order to have a beneficial impact on public health. To evaluate the potential [...] Read more.
In order to limit the disease burden and economic costs associated with the COVID-19 pandemic, it is important to understand how effective and widely distributed a vaccine must be in order to have a beneficial impact on public health. To evaluate the potential effect of a vaccine, we developed risk equations for the daily risk of COVID-19 infection both currently and after a vaccine becomes available. Our risk equations account for the basic transmission probability of COVID-19 (β) and the lowered risk due to various protection options: physical distancing; face coverings such as masks, goggles, face shields or other medical equipment; handwashing; and vaccination. We found that the outcome depends significantly on the degree of vaccine uptake: if uptake is higher than 80%, then the daily risk can be cut by 50% or more. However, if less than 40% of people get vaccinated and other protection options are abandoned—as may well happen in the wake of a COVID-19 vaccine—then introducing even an excellent vaccine will produce a worse outcome than our current situation. It is thus critical that effective education strategies are employed in tandem with vaccine rollout. Full article
(This article belongs to the Special Issue Vaccines: Uptake and Equity in Times of the COVID-19 Pandemic)
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Editorial
Flu RNA Vaccine: A Game Changer?
Vaccines 2020, 8(4), 760; https://doi.org/10.3390/vaccines8040760 - 14 Dec 2020
Cited by 2 | Viewed by 1877
Abstract
Influenza virus infection is a major One Health concern worldwide [...] Full article
(This article belongs to the Section Influenza Virus Vaccines)
Article
GspD, The Type II Secretion System Secretin of Leptospira, Protects Hamsters against Lethal Infection with a Virulent L. interrogans Isolate
Vaccines 2020, 8(4), 759; https://doi.org/10.3390/vaccines8040759 - 14 Dec 2020
Cited by 1 | Viewed by 1095
Abstract
The wide variety of pathogenic Leptospira serovars and the weak protection offered by the available vaccines encourage the search for protective immunogens against leptospirosis. We found that the secretin GspD of the type II secretion system (T2S) of Leptospira interrogans serovar Canicola was [...] Read more.
The wide variety of pathogenic Leptospira serovars and the weak protection offered by the available vaccines encourage the search for protective immunogens against leptospirosis. We found that the secretin GspD of the type II secretion system (T2S) of Leptospira interrogans serovar Canicola was highly conserved amongst pathogenic serovars and was expressed in vivo during infection, as shown by immunohistochemistry. Convalescent sera of hamsters, dogs, and cows showed the presence of IgG antibodies, recognizing a recombinant version of this protein expressed in Escherichia coli (rGspDLC) in Western blot assays. In a pilot vaccination study, a group of eight hamsters was immunized on days zero and 14 with 50 µg of rGspDLC mixed with Freund’s incomplete adjuvant (FIA). On day 28 of the study, 1,000 LD50 (Lethal Dose 50%) of a virulent strain of Leptospira interrogans serovar Canicola (LOCaS46) were inoculated by an intraoral submucosal route (IOSM). Seventy-five percent protection against disease (p = 0.017573, Fisher’s exact test) and 50% protection against infection were observed in this group of vaccinated hamsters. In contrast, 85% of non-vaccinated hamsters died six to nine days after the challenge. These results suggest the potential usefulness of the T2S secretin GspD of Leptospira as a protective recombinant vaccine against leptospirosis. Full article
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Article
Lactobacilli Expressing Broadly Neutralizing Nanobodies against HIV-1 as Potential Vectors for HIV-1 Prophylaxis?
Vaccines 2020, 8(4), 758; https://doi.org/10.3390/vaccines8040758 - 13 Dec 2020
Cited by 1 | Viewed by 1241
Abstract
In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual [...] Read more.
In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual HIV-1 transmission in high-risk cohorts, as a continuous high level of active bnAbs may be difficult to achieve at the primary site of sexual transmission, the human vagina with its acidic pH. Therefore, we used Lactobacillus, a natural commensal in the healthy vaginal microbiome, to express bn nanobodies (VHH) against HIV-1 that we reported previously. After demonstrating that recombinant VHHA6 expressed in E. coli was able to protect humanized mice from mucosal infection by HIV-1Bal, we expressed VHHA6 in a soluble or in a cell-wall-anchored form in Lactobacillus rhamnosus DSM14870. This strain is already clinically applied for treatment of bacterial vaginosis. Both forms of VHHA6 neutralized a set of primary epidemiologically relevant HIV-1 strains in vitro. Furthermore, VHHA6 was still active at an acidic pH. Thus, lactobacilli expressing bn VHH potentially represent an attractive vector for the passive immunization of women in cohorts at high risk of HIV-1 transmission. Full article
(This article belongs to the Section HIV Vaccines)
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Article
Repertoires of Vaccine Refusal in Romania
Vaccines 2020, 8(4), 757; https://doi.org/10.3390/vaccines8040757 - 13 Dec 2020
Cited by 1 | Viewed by 1164
Abstract
Repertoires are basic analytic units in discourse analysis and discursive psychology, characterized as repeatable building blocks speakers use for constructing versions of actions. In this study my aim is to analyze public repertoires which are available to parents as discursive resources to substantiate [...] Read more.
Repertoires are basic analytic units in discourse analysis and discursive psychology, characterized as repeatable building blocks speakers use for constructing versions of actions. In this study my aim is to analyze public repertoires which are available to parents as discursive resources to substantiate their decision not to vaccinate their children. Online content, two televised talk shows and a series of interviews with parents who refused vaccination from 2017–2019 were analyzed. As a result of this analysis, I have identified a series of repertoires such as distrust repertoires, rejecting any risks when it comes to children, vaccine ineffectiveness and ‘immunity is a limited resource that should not be forced’. These repertoires do a discursive work that seem to go beyond signs of concern or challenges to vaccine safety to perform a moral and epistemic delegitimization of the current system of medical services, medical research and government authorities. Moreover, the identification of the repertoires that circulate in the public space as resources fulfil a discursive function of replacing the current system with new moral and epistemic perspectives. Full article
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Article
Comparative Immunological Study in Mice of Inactivated Influenza Vaccines Used in the Russian Immunization Program
Vaccines 2020, 8(4), 756; https://doi.org/10.3390/vaccines8040756 - 12 Dec 2020
Viewed by 947
Abstract
A series of commercial inactivated influenza vaccines (IIVs) used in the Russian National Immunization Program were characterized to evaluate their protective properties on an animal model. Standard methods for quantifying immune response, such as hemagglutination inhibition (HAI) assay and virus neutralization (VN) assay, [...] Read more.
A series of commercial inactivated influenza vaccines (IIVs) used in the Russian National Immunization Program were characterized to evaluate their protective properties on an animal model. Standard methods for quantifying immune response, such as hemagglutination inhibition (HAI) assay and virus neutralization (VN) assay, allowed us to distinguish the immunogenic effect of various IIVs from that of placebo. However, these standard approaches are not suitable to determine the role of various vaccine components in immune response maturation. The expanded methodological base including an enzyme-linked immunosorbent assay (ELISA) and a neuraminidase ELISA (NA-ELISA) helped us to get wider characteristics and identify the effectiveness of various commercial vaccines depending on the antigen content. Investigations conducted showed that among the IIVs tested, Ultrix®, Ultrix® Quadri and VAXIGRIP® elicit the most balanced immune response, including a good NA response. For Ultrix®, Ultrix® Quadri, and SOVIGRIPP® (FORT LLC), the whole-virus specific antibody subclass IgG1, measured in ELISA, seriously prevailed over IgG2a, while, for VAXIGRIP® and SOVIGRIPP® (NPO Microgen JSC) preparations, the calculated IgG1/IgG2a ratio was close to 1. So, the immune response varied drastically across different commercial IIVs injected in mice. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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Article
Ginseng Stem-Leaf Saponins in Combination with Selenium Promote the Immune Response in Neonatal Mice with Maternal Antibody
Vaccines 2020, 8(4), 755; https://doi.org/10.3390/vaccines8040755 - 11 Dec 2020
Viewed by 904
Abstract
Neonates acquire from their mothers maternal antibody (MatAb) which results in poor immune response to vaccination. We previously demonstrated that ginseng stem-leaf saponins in combination with selenium (GSe) had adjuvant effect on the immune response to an attenuated pseudorabies virus (aPrV) vaccine. The [...] Read more.
Neonates acquire from their mothers maternal antibody (MatAb) which results in poor immune response to vaccination. We previously demonstrated that ginseng stem-leaf saponins in combination with selenium (GSe) had adjuvant effect on the immune response to an attenuated pseudorabies virus (aPrV) vaccine. The present study was to evaluate GSe for its effect on the immune response to aPrV vaccine in neonatal mice with MatAb. Results showed that GSe had adjuvant effect on the immune response to aPrV vaccine in neonates. When GSe was co-administered with aPrV vaccine (aP-GSe), specific gB antibody, Th1 cytokines (IL-2, IL-12 and IFN-γ) and Th2 cytokines (IL-4, IL-6 and IL-10) responses were significantly increased in association with enhanced protection of vaccinated neonates against the lethal PrV challenge even though MatAb existed when compared to the neonates immunized with aPrV vaccine alone. GSe-enhanced immune response depended on its use in the primary immunization. The mechanisms underlying the adjuvant effect of GSe may be due to more innate immune related pathways activated by GSe. Transcriptome analysis of splenocytes from neonates immunized with aP-GSe, aPrV or saline solution showed that there were 3976 differentially expressed genes (DEGs) in aP-GSe group while 5959 DEGs in aPrV group when compared to the control. Gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that innate immune responses and cytokine productions related terms or pathways were predominantly enriched in aP-GSe group, such as “NOD-like receptor signaling pathway”, “Natural killer cell mediated cytotoxicity”, “NF-κB signaling pathway”, “cytokine-cytokine receptor interaction”, and “Th1 and Th2 cell differentiation”. Considering the potent adjuvant effect of GSe on aPrV vaccine in neonatal mice with MatAb, it deserves further investigation in piglets. Full article
(This article belongs to the Section Vaccine Adjuvants)
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